首页> 外文期刊>Life sciences >Regulation of MMP-9 (gelatinase B) in activated human monocyte/macrophages by two different types of bisphosphonates.
【24h】

Regulation of MMP-9 (gelatinase B) in activated human monocyte/macrophages by two different types of bisphosphonates.

机译:两种不同类型的双膦酸酯对活化的人单核细胞/巨噬细胞中MMP-9(明胶酶B)的调节。

获取原文
获取原文并翻译 | 示例
           

摘要

Metalloproteinases (MMP), particularly MMP-9 produced by the intratumor monocyte/macrophages, play an important role in tumor invasion and metastases. Recent clinical trials in patients with primary breast cancer suggest that bisphosphonates (BP), above all clodronate, may reduce bone metastases. The aim of the present study was to evaluate whether the effects of BPs on cancer dissemination include inhibition of MMP-9 production in human monocyte/macrophages. The effects of clodronate and pamidronate on the MMP-9 expression in and secretion from stimulated human monocyte/macrophages were measured using quantitative reverse transcriptase - polymerase chain reaction (RT-PCR) and enzyme-linked immunoadsorbent assay (ELISA), respectively. The MMP-9 mRNA levels remained relatively stable in the presence of clodronate. In contrast, pamidronate at 30 microM-300 microM increased the mRNA levels 5- to 10-fold. MMP-9 secretion was dose-dependently down-regulated by clodronate whereas pamidronate at 30 microM induced a 50% increase on MMP-9 secretion (p < 0.05), followed by a down-regulation at higher concentrations. The results suggest that MMP-9 is differentially regulated at mRNA and enzyme protein level by BPs, which affect ATP-dependent intracellular enzymes (clodronate) or post-translational modification of GTPases (pamidronate). These findings may have implications for the therapeutic use of these compounds.
机译:金属蛋白酶(MMP),特别是由肿瘤内单核细胞/巨噬细胞产生的MMP-9,在肿瘤的侵袭和转移中起重要作用。最近在原发性乳腺癌患者中进行的临床试验表明,双膦酸盐(BP)首先是氯膦酸盐,可以减少骨转移。本研究的目的是评估BP对癌症传播的影响是否包括抑制人单核细胞/巨噬细胞中MMP-9的产生。使用定量逆转录酶-聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)分别测量了氯膦酸盐和帕米膦酸盐对受刺激的人单核细胞/巨噬细胞中MMP-9表达和分泌的影响。在氯膦酸盐存在下,MMP-9 mRNA水平保持相对稳定。相反,帕米膦酸在30 microM-300 microM时将mRNA水平提高5至10倍。 MMP-9分泌受氯膦酸盐剂量依赖性下调,而帕米膦酸30 microM引起MMP-9分泌增加50%(p <0.05),随后较高浓度下调。结果表明,MMP-9在BP的mRNA和酶蛋白水平上受到差异调节,从而影响ATP依赖的细胞内酶(氯膦酸盐)或GTPases的翻译后修饰(帕米膦酸)。这些发现可能对这些化合物的治疗用途有影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号